The findings of this study indicate that loss to follow-up is slightly higher in the diagnosis period than the pre-treatment period. Once diagnosed with TB, two thirds of patients initiate TB treatment on time. However in total, 79 sputum smear-positive pulmonary cases had a delayed start to treatment, with a mean delay of 7 days.
We observed 8% loss to follow-up during the diagnostic period and nearly 5%in the pre-treatment period. However, another study in Pakistan reported 12.9% loss to follow up, of which nearly 5.2% was pre-treatment . In similar studies in Pakistan, Fatima et al. (2011), Rao et al. (2011) and Rao et al. (2009) reported 16,145, 7467 and 869 presumptive cases respectively. Of these, the respective LTFU rates were 6%, 15% and 28% [14,15,16]. Moreover, in other Asian countries, such as India , Vietnam  and Tajikistan  LTFU rates have been recorded as 4%, 8% and 18%, respectively. Loss to follow-up rate in the private sector who report to Pakistan’s National TB Control Programme is slightly lower, probably because of the oversight approach employed. At field or district level, focal persons from public and private sides hold regular quarterly meetings to keep track of the performance. To support this, a district-level TB register is maintained by field staff and it is ensured that no patient is dropped during the TB care pathway.
Patient counselling is seen as important intervention to reduce LTFU, however, it is unclear whether counselling has influenced our results. In one study in Pakistan, patient counselling did not impact on the rate of LTFU . Other studies have shown that behavioral counselling integrated with TB care generated better adherence to treatment protocols overall [20, 21] and patients perceive counselling as a valuable inclusion in TB control programmes, especially when counselling is combined with financial support .
Addressing communication gaps among TB clinics, laboratories and patients may be one solution to these types of programmatic problems . The emerging mHealth technologies may possibly bridge the communication gap between health care providers and patients and could reduce the rate of LTFU [23, 24], for example, text message-based interventions [25, 26]. However, to allow improved mobile phone communication to happen, contact details need to be complete in TB registers, which is often not the case .
Another possible reason for LTFU is that people with presumptive TB need to wait for results. In a discussion paper where 100 hypothetical patients were diagnosed with TB, Davis et al. (2012) found that same-day diagnosis increased the chance of treatment initiation when compared to sputum collection over one or two days, with reporting of results afterwards . Moreover, a meta-analysis of eight studies revealed that the sensitivity of same-day sputum microscopy versus standard smear microscopy was similar . Furthermore, advancements in mobile phone based microscopy may also offer great opportunities to facilitate timely interpretation and communication of sputum smear results [30, 31].
The use of molecular diagnostic tests and same day reporting and TB treatment initiation may also reduce LTFU. In the districts in which we carried out our study, microscopy remains the mainstay of diagnosis. Considering the microscopy-specific diagnostic algorithm, the introduction and roll out of molecular tests such as the Xpert MTB/RIF test is promising . The Xpert MTB/RIF test provides quick and accurate diagnosis that can potentially reduce delays and dropouts during the diagnostic process . For example, the median time to treatment initiation for patient diagnosed using Xpert MTB/RIF in South Africa was 0 days, whereas, for other forms of diagnosis using radiology and culture, the median times to treatment initiation were 14 days and 144 days, respectively .
We studied loss to follow up during the diagnosis period and then before treatment initiation. During the diagnostic period, more males were lost compared to females. In another study, carried out in one district of Pakistan, 3.4% more males were lost, than females (16.5% vs 13.1%) . There are well recognized differences in the gender ratio of TB patients, with males outnumbering females by 12% . These differences may be due to health seeking behavior and socio-economic factors. For example, Malawian females are more conscious about their health and would visit a healthcare facility earlier than men . However, men may also be given priority over women when accessing healthcare facilities [37, 38]. Additionally, lower TB case notification rates among women may be due to stigma, restricted access to financial resources and traditional beliefs [38,39,40]. Higher case notification rates among men may also be due to a higher prevalence of risk factors for TB among men, such as cigarette smoking, exposure to silica dust, etc. .
The strength of this study is a rigorous approach of case ascertainment across three TB registers, i.e., the referral register, the diagnostic register and the TB treatment register. However, missing data was a limitation of the study. We also focused on pulmonary TB and sputum smear positive TB only and did not include information on referral, diagnosis and treatment for clinically diagnosed pulmonary patients and extra-pulmonary TB patients. Additionally, people who were lost to follow up were not tracked in TB registers of the neighboring districts to ascertain if the patients accessed care elsewhere, and might have initiated their TB treatment elsewhere. In addition, including “well performing” private care providers in a sample, we may have biased our findings, which could be different if a representative sample of private care providers was taken. As, our study used a non-representative sample, so it may be difficult to generalize our findings to the whole of Pakistan.